PMID- 31173224
OWN - NLM
STAT- MEDLINE
DCOM- 20191211
LR  - 20211204
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 20
IP  - 2
DP  - 2019 Aug
TI  - Role of the PI3K‑mTOR autophagy pathway in nerve damage in rats with intermittent 
      hypoxia‑aggravated whole brain ischemia.
PG  - 1411-1417
LID - 10.3892/mmr.2019.10337 [doi]
AB  - The present study aimed to compare the expression of phosphatidylinositol 
      3‑kinase (PI3‑K), mammalian target of rapamycin (mTOR) and Beclin‑1 between the 
      hippocampi of normal rats and intermittent ischemic rats following whole brain 
      ischemia/reperfusion (I/R), and investigate the role of the PI3K‑mTOR autophagy 
      pathway in rat nerve damage following intermittent hypoxia (IH)‑aggravated whole 
      brain ischemia. A total of 80 male Wistar rats were divided by random number 
      table into a sham operation group (SO group; 20 rats), pure cerebral 
      ischemia/reperfusion group (I/R group; 20 rats), intermittent hypoxia for 7 
      days‑I/R group (IH7+I/R group; 20 rats) and intermittent hypoxia for 21 days‑IR 
      group (IH21+I/R group; 20 rats). Prior to model establishment, the rats in the 
      IH7+I/R group and IH21+I/R group underwent intermittent hypoxia for 7 and 21 
      days, respectively. The optimized Pulsinelli 4‑vessel occlusion method was used 
      to prepare the I/R model. H&E staining and transmission electron microscopy were 
      performed to observe the morphological changes of nerve cells in the hippocampus. 
      Immunohistochemical and reverse transcription‑quantitative polymerase chain 
      reaction (RT‑qPCR) analyses were performed to detect the expression levels of 
      PI3‑K, mTOR and Beclin‑1 in the hippocampal brain tissues of the rats. A Morris 
      water maze test was used to assess rat learning and memory. The results showed 
      that, compared with the SO group, the rats in the I/R group exhibited structural 
      damage in neurons (shown by H&E staining), a reduced number of viable nerve 
      cells, and decreased learning and memory ability at each time point. The results 
      of the immunohistochemical analysis showed that the numbers of PI3‑K, mTOR and 
      Beclin‑1 immunopositive cells were increased (P<0.05). The RT‑qPCR analysis 
      showed increased expression levels of PI3‑K, mTOR and Beclin‑1 (P<0.05). Compared 
      with the I/R group, the rats in the IH‑I/R groups exhibited aggravated structural 
      damage in neurons, shown by H&E staining and electron microscopy. The number of 
      viable nerve cells was decreased, and the rats exhibited decreased learning 
      ability and memory. The immunohistochemical analysis revealed that the numbers of 
      PI3‑K, mTOR and Beclin‑1 immunopositive cells were increased (P<0.05). The 
      RT‑qPCR analysis showed increased expression levels of PI3‑K, mTOR and Beclin‑1 
      (P<0.05). The above changes were more marked in the IH21+I/R group (P<0.05). 
      Taken together, IH was shown to aggravate nerve damage following whole brain I/R. 
      The underlying mechanism was associated with activation of the 
      PI3K‑mTOR‑autophagy pathway and increased loss of nerve cells.
FAU - Guo, Xia
AU  - Guo X
AD  - Department of Respiratory Medicine, Affiliated Hospital of North China University 
      of Science and Technology, Tangshan, Hebei 063000, P.R. China.
FAU - Liu, Yao
AU  - Liu Y
AD  - Department of Rehabilitation, College of Nursing and Rehabilitation, North China 
      University of Science and Technology, Tangshan, Hebei 063000, P.R. China.
FAU - Zhao, Yaning
AU  - Zhao Y
AD  - Department of Rehabilitation, College of Nursing and Rehabilitation, North China 
      University of Science and Technology, Tangshan, Hebei 063000, P.R. China.
FAU - Fan, Rong
AU  - Fan R
AD  - Department of Rehabilitation, College of Nursing and Rehabilitation, North China 
      University of Science and Technology, Tangshan, Hebei 063000, P.R. China.
FAU - Bai, Yali
AU  - Bai Y
AD  - Department of Rehabilitation, College of Nursing and Rehabilitation, North China 
      University of Science and Technology, Tangshan, Hebei 063000, P.R. China.
FAU - Guo, Xiangfei
AU  - Guo X
AD  - Department of Rehabilitation, College of Nursing and Rehabilitation, North China 
      University of Science and Technology, Tangshan, Hebei 063000, P.R. China.
FAU - Li, Jianmin
AU  - Li J
AD  - Department of Respiratory Medicine, Affiliated Hospital of North China University 
      of Science and Technology, Tangshan, Hebei 063000, P.R. China.
FAU - Chen, Changxiang
AU  - Chen C
AD  - Department of Rehabilitation, College of Nursing and Rehabilitation, North China 
      University of Science and Technology, Tangshan, Hebei 063000, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20190604
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - *Autophagy
MH  - Hypoxia-Ischemia, Brain/*metabolism/*pathology
MH  - Male
MH  - Maze Learning
MH  - Neurons/pathology/ultrastructure
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Rats, Wistar
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
EDAT- 2019/06/08 06:00
MHDA- 2019/12/18 06:00
CRDT- 2019/06/08 06:00
PHST- 2016/04/13 00:00 [received]
PHST- 2017/03/28 00:00 [accepted]
PHST- 2019/06/08 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2019/06/08 06:00 [entrez]
AID - 10.3892/mmr.2019.10337 [doi]
PST - ppublish
SO  - Mol Med Rep. 2019 Aug;20(2):1411-1417. doi: 10.3892/mmr.2019.10337. Epub 2019 Jun 
      4.